Essential role of phosphoinositide metabolism in synaptic vesicle recycling

Cell. 1999 Oct 15;99(2):179-88. doi: 10.1016/s0092-8674(00)81649-9.


Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates. We report here that synaptojanin 1-deficient mice exhibit neurological defects and die shortly after birth. In neurons of mutant animals, PI(4,5)P2 levels are increased, and clathrin-coated vesicles accumulate in the cytomatrix-rich area that surrounds the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation followed by delayed recovery. These results provide genetic evidence for a crucial role of phosphoinositide metabolism in synaptic vesicle recycling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell-Free System
  • Cerebral Cortex / metabolism
  • Coated Pits, Cell-Membrane / metabolism
  • Endocytosis
  • Enzyme Inhibitors / metabolism
  • Exons
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Membrane Potentials
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Nerve Endings / metabolism
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Phosphatidylinositols / metabolism*
  • Phosphoric Monoester Hydrolases / deficiency
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure


  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Phosphatidylinositols
  • synaptojanin
  • Phosphoric Monoester Hydrolases